My long term goal is to better understand the pharmacology of the drugs of abuse in the developing fetus. This requires a comprehensive study of the pharmacokinetics of the drug in the maternal-fetal unit, the pharmacodynamics of the drug on the mother and fetus, and its mechanisms of action. My research efforts, so far, have concentrated on the pharmacokinetics and pharmacodynamic effects of opiates and marijuana in the ovine maternal-fetal unit. My plans for the next 5 years are to investigate the mechanisms of action of morphine in the fetus and to explore some of the possible reasons that may account for the more pronounced excitatory action of morphine in the fetus. It is proposed that the multiple actions of morphine on fetal neurobehavior and cardiorespiratory function may be mediated by different opiate receptor subtypes, and that differences between morphine's action in the fetus and adult may be due to differences in the proportion of the various subtypes of opiate receptors in the fetal brain and adrenal. It is also proposed that the more pronounced excitatory action of morphine in the fetus may be due to a lower proportion of enkephalin peptides to catecholamines in the fetal adrenal medulla. The testing of these hypotheses would require different techniques that are currently not available in my laboratory, such as receptor binding techniques and peptide quantitation. It is my intention to seek advice from, and work closely with, investigators who are actively involved in these areas. These expertise are available within our department. It is also my plan to continue my effort in directing a consortium project to study the effects of marijuana smoke exposure during pregnancy. This is a multidisciplinary project involving a number of investigators from other institutions. Our plan is to investigate the mechanisms by which prenatal marijuana smoke exposure results in intrauterine growth retardation and premature labor.